[MUSIC] >> Hello, welcome. Do our children inherit the impact of our life experiences as well as our genes? Now we descend to my easy crazy question 15 years ago, but today the answer is yes. We now know that if we're stressed, if we eat too much or too little, if we smoke, if we're exposed to toxins, then we can acquire characteristics and pass them down to children and even grandchildren. The idea of epigenetics as it's called, the parents don't just pass their genes to their children. A subtle differences in the way those genes operate is one of the fastest growing areas of scientific study. Well, we can't experiment with people in the lab. We have some accidental experiments that use topical events as a way of studying epigenetic changes. Back in the winter of 1944 to 1945, the Nazis occupied Holland. When in lowering resources, the Nazis diverted all of the food to themselves. It's known historically as the Dutch Hunger Winter. Holland went from a rich European country, well fed, to a situation with less than 1,000 calories a day. 18,000 people died of malnutrition. But what happened to those who were fetuses at the time? What happened was a phenomena called fetal programming. It turned out that he fetuses during the Dutch Hunger Winter, reprogrammed their metabolism in the second and third trimesters. The fetus was sitting in the uterus, and physiologically it was asking, what's the environment like out there? Well, not a lot of nutrition coming in, so it programmed it's metabolism to be thrifty. A metabolism designed to store things away. If you get the fetus a little bit of sugar, then for the rest of its existence it doesn't waste it but it stores it away. If it gets salt it doesn't throw it away in the urine, it keeps it. Well, how does this thrifty metabolism cope when confronted with the Western diet? You've got a body trying to be as efficient as possible at storing calories since there wasn't much food around during your development. Well, that's gonna work well until suddenly you have all the food you need and more. Once you have too many calories, or even simply enough calories, your body can't stop storing calories. That's gonna cause you to suffer a range of disorders including obesity and diabetes. What about when pregnant? Well, for a typical amount of food eaten by the mother, the mother's gonna be atypically good at keeping it for herself. So the baby's gonna end up subtly malnourished. Does all this bother you about what life was like for you as a fetus? Anyone who has reproduced or even in a fetus can find this literature unnerving. But perhaps you can also see how adaptive fetal programming could be in nature. The fetus is adapting to conditions in the world it's likely going to grow up in. So a question now is, what is the mechanism that allows physiology to respond to the environment. To help get an answer, here is a revelation from genomics. A revelation that made me in interpreting your personal genome so also gonna require that you be able to access your parents DNA. In late 2009, scientists at DECODE, a company that specializes in analyzing the human genome, reported that in some common diseases, which parent the risk allele came from made a difference. In other words, an allele could predispose someone to type 2 diabetes when inherited from dad. But the same allele actually protected against type 2 diabetes when it was inherited from mom. Well, that told us that male and female genomes were chemically modified in different ways. A lot of other examples have been found where key genes are active or not, depending on whether they're from your mom or dad. And in the jargon of the genetics trade, we say these genes, that they are imprinted. Genomic imprinting is an extreme example of epigenetics. Epigenetics then is the study of how the activity of genes can be altered without changing the genetic code itself. Epigenetics is from the Greek, it means on top of genetics. It is in addition to genetics. It's not instead of genetics, it is in addition to genetics. In recent years, epigenetics has emerged as a consistent theme in the media in its coverage of genetics. There is a view that a trait has to be determined by nature or by nurture. There is a love of deterministic arguments out there. I think in our culture as well as science, we like to think that everything is learned or everything is inborn. And the fact that it's often a little bit of both just isn't such a good story. And epigenetics deals with the age old question of nature and nurture, and notice that I don't say versus. Scientists gave up the notion of nature and nurture being in conflict decades ago, they spotted that cliche persisting in the public eye. The big insight of epigenetics is that genes are agents of nurture as well as nature. The way epigenetics and imprinting happen is through methylation. The addition of a mephogle, which is a carbon atom plus three hydrogen atoms, through a particular basis in the DNA sequence. This acts as an instruction to turn a gene off. Epigenetics means that the sequence of the DNA doesn't change, but access to the DNA changes biochemically. And crucially, this altered DNA can then be passed down to children and grandchildren. So a brief molecular biology interlude with this figure. Access to DNA is changed by adding methyl groups to the DNA or by chemically modifying the histone proteins the DNA is wrapped around. You have six billion nucleotides in a cell which, together, would stretch out for six feet. That being the DNA around those histones is evolution's answer as to how you get all that DNA into a tiny little nucleus. The DNA is methylated and the DNA gets so tightly wrapped up It's closed for business, now that the protein's required to switch on the gene and get access to the DNA. Dr Brands told you to think of the sequences of DNA as words in a book. You can change the book's story if you staple or stick some of the pages together. We don't change any of the words here, but you can no longer read certain pages, and that can change the entire story. Well, methylation is like a staple. It stops the cell from reading genes. Now you might be thinking that it sounds like quintessential bad news to shut a whole lot of genes down. That isn't necessarily so, because gene activity is context dependent, if you're a brain cell, the last thing you want is muscle proteins or liver proteins being made inside you. So you want all the genes that produce these proteins firmly methylated and therefore switched off. What gets methylated where and when will of course be subject to evolution. The prefrontal cortexes of human brains are much less methylated than those of chimps. So there'd be more gene activity in our brains. And this suggests that differences in methylation could be an important clue to human primate evolution. On the other hand, we also happen to be far more susceptible to cancer than chimps. Cancers typically lose most of the methylation on their DNA so that all sorts of genes are inappropriately switched on, linked genes that tell the cells to divide. Uncontrolled cell division is what makes cancer so dangerous. Cancers involve DNA changes that happen in you. We all have patents of DNA mutation that passed down through the generations. Custom to inhabitants, changing by mutational changes in the DNA sequence, but now we know about this non-DNA inhabitants. [SOUND]
